{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q8N2W9","secondaryAccessions":["O75926","Q96G19","Q9UN16"],"uniProtkbId":"PIAS4_HUMAN","entryAudit":{"firstPublicDate":"2003-09-19","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2002-10-01","entryVersion":208,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"E3 SUMO-protein ligase PIAS4"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12511558"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12631292"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12727872"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15831457"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15976810"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22508508"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32832608"}],"value":"2.3.2.27"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"11388671"}],"value":"PIASy"}},{"fullName":{"value":"Protein inhibitor of activated STAT protein 4"}},{"fullName":{"value":"Protein inhibitor of activated STAT protein gamma"},"shortNames":[{"value":"PIAS-gamma"}]}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"32832608"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:17002"}],"value":"PIAS4"},"synonyms":[{"value":"PIASG"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JM05"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11248056"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11388671"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12223491"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12511558"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12631292"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12727872"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12750312"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15831457"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15976810"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16617055"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21965678"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22508508"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32832608"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34048572"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35013556"}],"value":"Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor (PubMed:12511558, PubMed:12631292, PubMed:12727872, PubMed:15831457, PubMed:15976810, PubMed:22508508, PubMed:32832608). Mediates sumoylation of ALKBH5, AXIN1, CEBPA, KLF8, GATA2, PARK7, HERC2, MYB, TCF4 and RNF168 (PubMed:12223491, PubMed:12511558, PubMed:12631292, PubMed:12727872, PubMed:12750312, PubMed:15831457, PubMed:15976810, PubMed:16617055, PubMed:22508508, PubMed:34048572). Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway (PubMed:11388671). Involved in gene silencing (PubMed:11248056). In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations (PubMed:12727872, PubMed:15831457). Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation (PubMed:21965678). Binds to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs) (By similarity). Catalyzes conjugation of SUMO2 to KAT5 in response to DNA damage, facilitating repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:32832608). Mediates sumoylation of PARP1 in response to PARP1 trapping to chromatin (PubMed:35013556). Mediates sumoylation of KLF8, repressing KLF8 transcriptional activity and cell cycle progression into G(1) phase (PubMed:16617055). Sumoylates ALKBH5 downstream of MAPK8/JNK1 and MAPK9/JNK2 in response to reactive oxygen species (ROS), inhibiting ALKBH5 RNA demethylase activity (PubMed:34048572)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.","ecNumber":"2.3.2.27","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12511558"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12631292"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12727872"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15831457"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15976810"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22508508"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32832608"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34048572"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35013556"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12511558"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12631292"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12727872"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15831457"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15976810"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21965678"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22508508"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32832608"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34048572"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35013556"}],"value":"Protein modification; protein sumoylation"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JM05"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11248056"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11388671"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11439351"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15251447"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21965678"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28842558"}],"value":"Interacts with AR, GATA2, LEF1, TP53 and STAT1 (IFNG-induced) (PubMed:11248056, PubMed:11388671, PubMed:11439351). Interacts with TICAM1 (PubMed:15251447). Interacts with MTA1 (PubMed:21965678). Interacts with PRDM1/Blimp-1 (PubMed:28842558). Interacts with TRIM32 upon treatment with UVB and TNF (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"O43865","geneName":"AHCYL1","intActId":"EBI-2371423"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"P05067","geneName":"APP","intActId":"EBI-77613"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"Q14457","geneName":"BECN1","intActId":"EBI-949378"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"Q96IK1-2","geneName":"BOD1","intActId":"EBI-18924329"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"P27797","geneName":"CALR","intActId":"EBI-1049597"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"Q8N5S9-2","geneName":"CAMKK1","intActId":"EBI-25850646"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"Q6ZP82-1","geneName":"CCDC141","intActId":"EBI-49119542"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"P12830","geneName":"CDH1","intActId":"EBI-727477"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"Q15078","geneName":"CDK5R1","intActId":"EBI-746189"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"Q8IUI8","geneName":"CRLF3","intActId":"EBI-2872414"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"P36957","geneName":"DLST","intActId":"EBI-351007"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"O00472","geneName":"ELL2","intActId":"EBI-395274"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"P11474","geneName":"ESRRA","intActId":"EBI-372412"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"Q6P1L5","geneName":"FAM117B","intActId":"EBI-3893327"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"Q8TAK5","geneName":"GABPB2","intActId":"EBI-8468945"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"F2Z2M7","geneName":"GALNT10","intActId":"EBI-23893155"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"P15976-2","geneName":"GATA1","intActId":"EBI-9090198"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"Q9Y4H4","geneName":"GPSM3","intActId":"EBI-347538"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"Q16665","geneName":"HIF1A","intActId":"EBI-447269"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"P09017","geneName":"HOXC4","intActId":"EBI-3923226"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"P42858","geneName":"HTT","intActId":"EBI-466029"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"P80217-2","geneName":"IFI35","intActId":"EBI-12823003"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q8N2W9","intActId":"EBI-473160"},"interactantTwo":{"uniProtKBAccession":"Q9UKP3-2","geneName":"ITGB1BP2","intActId":"EBI-25856470"},"number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LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12727872"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15831457"}],"value":"Colocalizes with SUMO1 and TCF7L2/TCF4 and LEF1 in a subset of PML (promyelocytic leukemia) nuclear bodies"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11248056"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12727872"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15831457"}],"value":"Nucleus, PML body","id":"SL-0465"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11439351"}],"value":"Highly expressed in testis and, at lower levels, in spleen, prostate, ovary, colon and peripheral blood leukocytes"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11248056"}],"value":"The LXXLL motif is a coregulator signature that is essential 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